Lifetime Cumulative Exposure Research Articles

Smoking status is associated with mild cognitive impairment assessed with the mini-mental state examination in Japanese diabetic patients.

We assessed the association between smoking status and mild cognitive impairment (MCI) in Japanese diabetic patients. This cross-sectional study included 323 diabetic patients, aged 40-79years, who were referred to an outpatient diabetic clinic between January and July 2013 at Shiga University of Medical Science Hospital (Otsu, Japan). Cognitive function was assessed using the mini-mental state examination (MMSE), and patients were classified into two categories: normal cognitive function (MMSE score≥27) and MCI (MMSE score 22-26). Logistic regression analysis was used to estimate the multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for MCI in current smokers and ex-smokers compared with never-smokers. Of the 323 patients, 55 (17.0%), 134 (41.5%), and 134 (41.5%) were current smokers, ex-smokers, and never-smokers, respectively. Of these, 68 (21.0%) patients had MCI. After adjusting for age, sex, systolic blood pressure, body mass index, high-density lipoprotein cholesterol, estimated glomerular filtration rate, hemoglobin A1c, insulin therapy, sulfonylurea, history of coronary heart disease, exercise habit, drinking status, and education, the OR for MCI was 3.62 (95% CI 1.26-10.40) in current smokers compared with never-smokers. In addition, the multivariable-adjusted ORs for MCI were 3.02 (95% CI 0.64-14.32) in current smokers <30.0 pack-years and 4.90 (95% CI 1.32-18.16) in current smokers ≥30.0 pack-years, compared with never-smokers (p for trend=0.017). Current smoking, especially current smoking for which cumulative lifetime exposure was high, was associated with MCI, as assessed using the MMSE in Japanese diabetic patients.

Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness.

Background: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinal MRI studies have been traditionally used to assess the issue of progression of brain abnormalities in schizophrenia, information from cross-sectional neuroimaging studies directly comparing first-episode and chronic schizophrenia patients to healthy controls may also be useful to further clarify this issue. With the recent interest in multisite mega-analyses combining structural MRI data from multiple centers aiming at increased statistical power, the present multisite voxel-based morphometry (VBM) study was carried out to examine patterns of brain structural changes according to the different stages of illness and to ascertain which (if any) of such structural abnormalities would be specifically correlated to potential clinical moderators, including cumulative exposure to antipsychotics, age of onset, illness duration and overall illness severity.Methods: We gathered a large sample of schizophrenia patients (161, being 99 chronic and 62 first-episode) and controls (151) from four previous morphometric MRI studies (1.5 T) carried out in the same geographical region of Brazil. Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8) software with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) algorithm. Group effects on regional gray matter (GM) volumes were investigated through whole-brain voxel-wise comparisons using General Linear Model Analysis of Co-variance (ANCOVA), always including total GM volume, scan protocol, age and gender as nuisance variables. Finally, correlation analyses were performed between the aforementioned clinical moderators and regional and global brain volumes.Results: First-episode schizophrenia subjects displayed subtle volumetric deficits relative to controls in a circumscribed brain regional network identified only in small volume-corrected (SVC) analyses (p < 0.05, FWE-corrected), including the insula, temporolimbic structures and striatum. Chronic schizophrenia patients, on the other hand, demonstrated an extensive pattern of regional GM volume decreases relative to controls, involving bilateral superior, inferior and orbital frontal cortices, right middle frontal cortex, bilateral anterior cingulate cortices, bilateral insulae and right superior and middle temporal cortices (p < 0.05, FWE-corrected over the whole brain). GM volumes in several of those brain regions were directly correlated with age of disease onset on SVC analyses for conjoined (first-episode and chronic) schizophrenia groups. There were also widespread foci of significant negative correlation between duration of illness and relative GM volumes, but such findings remained significant only for the right dorsolateral prefrontal cortex after accounting for the influence of age of disease onset. Finally, significant negative correlations were detected between life-time cumulative exposure to antipsychotics and total GM and white matter volumes in schizophrenia patients, but no significant relationship was found between indices of antipsychotic usage and relative GM volume in any specific brain region.Conclusion: The above data indicate that brain changes associated with the diagnosis of schizophrenia are more widespread in chronic schizophrenia compared to first-episode patients. Our findings also suggest that relative GM volume deficits may be greater in (presumably more severe) cases with earlier age of onset, as well as varying as a function of illness duration in specific frontal brain regions. Finally, our results highlight the potentially complex effects of the continued use of antipsychotic drugs on structural brain abnormalities in schizophrenia, as we found that cumulative doses of antipsychotics affected brain volumes globally rather than selectively on frontal-temporal regions.

Age at occupational exposure to combustion products and lung cancer risk among men in Stockholm, Sweden.

Occupational exposure to combustion products rich in polycyclic aromatic hydrocarbons and particles is associated with an increased risk of lung cancer. This study aimed to evaluate whether the risk depended on the age at which the individuals were exposed. Data from 1042 lung cancer cases and 2364 frequency-matched population controls selected from all men aged 40-75 years residing in Stockholm County, Sweden, at any time between 1985 and 1990, included detailed questionnaire information on occupational, residential, and smoking history. Occupational exposures were assessed by an occupational hygienist, and exposure to air pollution from road traffic was estimated based on dispersion models. We found that individuals exposed to combustion products in their twenties were at higher risk than those never exposed (adjusted OR = 1.46; 95% CI 1.02, 2.10). The association was still evident after adjusting for a number of potential confounders, including lifetime cumulative exposure and latency. No clear association was found in those exposed at older ages. Exposure to combustion products at a young age was associated with elevated risk of lung cancer. Exposure-reduction programs should be aware of the susceptibility of the younger employees.

Stress exposure and sensitivity in the clinical high-risk syndrome: Initial findings from the North American Prodrome Longitudinal Study (NAPLS)

There is inconsistent evidence for increased stress exposure among individuals at clinical high risk (CHR) for psychosis. Yet similar to patients with a diagnosed psychotic illness, the preponderance of evidence suggests that CHR individuals tend to experience stressful life events (LE) and daily hassles (DH) as more subjectively stressful than healthy individuals. The present study utilizes data from the North American Prodrome Longitudinal Study Phase 2 (NAPLS-2) to test the hypotheses that (1) CHR individuals manifest higher self-reported stress in response to both LE and DH when compared to healthy controls (HC), (2) group differences in self-reported stress increase with age, (3) baseline self-reported stress is associated with follow-up clinical status, and (4) there is a sensitization effect of LE on the response to DH. In contrast to some previous research, the present findings indicate that the CHR group (N=314) reported exposure to more LE when compared to the HC group (N=162). As predicted, CHR participants rated events as more stressful, and those who progressed to psychosis reported a greater frequency of LE and greater stress from events compared to those whose prodromal symptoms remitted. There was also some evidence of stress-sensitization; those who experienced more stress from LE rated current DH as more stressful. The results indicate that the “prodromal” phase is a period of heightened stress and stress sensitivity, and elevated cumulative lifetime exposure to stressful events may increase reactions to current stressors.

Deficits in Neurological and Neuropsychological Function vs. Cumulative Exposure to Manganese in Production Welders

Deficits in Neurological and Neuropsychological Function vs. Cumulative Exposure to Manganese in Production WeldersAbstract Number:2569 Frank S. Rosenthal*, Eric Ward, S. Elizabeth Zauber, Shalmali Dharmadhikari, Sandy Snyder, Jeffrey Bainter, Ruoyun Ma, Zaiyang Long, Chien-lin Yeh, Rosemarie Bowler, and Ulrike Dydak Frank S. Rosenthal* Purdue University School of Health Sciences, United States, E-mail Address: [email protected] Search for more papers by this author , Eric Ward Purdue University School of Health Sciences, United States, E-mail Address: [email protected] Search for more papers by this author , S. Elizabeth Zauber Department of Neurology, Indiana School of Medicine, United States, E-mail Address: [email protected] Search for more papers by this author , Shalmali Dharmadhikari Purdue University School of Health Sciences, United States, E-mail Address: [email protected] Search for more papers by this author , Sandy Snyder Purdue University School of Health Sciences, United States, E-mail Address: [email protected] Search for more papers by this author , Jeffrey Bainter Purdue University School of Health Sciences, United States, E-mail Address: [email protected] Search for more papers by this author , Ruoyun Ma E-mail Address: [email protected] Search for more papers by this author , Zaiyang Long Purdue University School of Health Sciences, United States, E-mail Address: [email protected] Search for more papers by this author , Chien-lin Yeh Purdue University School of Health Sciences, United States Search for more papers by this author , Rosemarie Bowler San Francisco State University, United States, E-mail Address: [email protected] Search for more papers by this author , and Ulrike Dydak Purdue University School of Health Sciences, United States, E-mail Address: [email protected] Search for more papers by this author AbstractDeficits in neurological and neuropsychological function have been associated with occupational exposure to manganese (Mn) in previous studies. We investigated the effect of cumulative exposure on neurological and neuropsychological function among welders. Cumulative lifetime and past-year Mn exposure of 26 production welders and 11 controls, all employed in a manufacturing facility, were estimated with a model combining work histories and air sampling. Welders and controls took a battery of tests, including tests of verbal fluency (Animal Naming, Fruit Naming), memory (Auditory Verbal Leaning Tests [AVLTs], Digit Span), visuospatial tracking (Trail Making tests A and B, Digit symbol) and motor function (Grooved Pegboard, Finger Tapping, Parallel Rating). Motor function was also evaluated with part 3 of the MDS-Unified Parkinson’s Disease Rating Scale (UPDRS). The mean cumulative exposure and years of welding of the welders was 2.09 ? 2.07[SD] mg/m3-y and 12.6 ? 7.8 y respectively. Compared to controls, welders performed less well on the Animal Naming test (36.1 vs 48.6, p = 0.04) and Parallel Rating test (2.92 vs. 1.27, p = 0.004). The mean UPDRS tended to be worse in welders vs. controls (7.04 v. 4.64, p = 0.07). Among welders, cumulative exposure was significantly or nearly significantly correlated with two of the AVLT tests, Trial 1 and Trial 5, (spearman’s rho [?] = -0.505, p = 0.008; ? = -0.382, p = 0.054, respectively). The UPDRS score, adjusted for age, was marginally correlated with cumulative exposure among welders (? = 0.35, p = 0.09). With past-year exposure, similar relationships were found with UPDRS scores, but not with the AVLT tests. The ability to see neurological and neuropsychological effects was limited by the small sample size. However, the results suggest early changes in verbal fluency, memory and motor function due to Mn exposure.

Abstract LB-283: A prospective study of breast cancer risk associated with occupational exposure to potentially endocrine disrupting compounds

Abstract Background: Endocrine disrupting compounds, exogenous substances that interfere with normal endocrine functions, have been suspected to play a role in the etiology of breast cancer. The purpose of this study was to investigate the relationship between occupational exposure to potential endocrine disrupting compounds and breast cancer risk among women enrolled in the Sister Study, a prospective cohort study of US and Puerto Rican women designed to examine the genetic and environmental risk factors for breast cancer. Methods: Over 50,000 women aged 33-74 enrolled in the Sister Study between 2004 and 2009. A comprehensive baseline questionnaire included questions about occupational exposures, including ever use and duration and frequency of use of nine agents containing potential endocrine disrupting compounds: Dyes or Inks, Gasoline or other Petroleum Products, Glues or Adhesives, Lubricating Oils, Metals, Paints, Pesticides, Organic Solvents, and Stains. Cumulative lifetime exposure to each potential endocrine disruptor was estimated and classified into quartiles. Study participants were prospectively followed from baseline until breast cancer diagnosis, death, or end of follow-up. Multivariable Cox proportional hazards regression was used to assess the impact of level of exposure (comparing each quartile of exposure with never exposure) to each of these compounds on breast cancer risk, adjusting for established breast cancer risk factors. Results: Among the 47,755 women in the Sister Study with an occupational history, a total of 1798 cases of invasive breast cancer were diagnosed. Compared to their respective never exposure groups, an elevated risk of estrogen-receptor positive breast cancer was observed for women in the top quartile of occupational exposure to Dyes or Inks (HR: 1.7, 95%CI: 1.1-2.8). Non-significantly elevated risks were observed for women in the top quartile of occupational exposure to Gasoline or other Petroleum Products (HR: 1.7, 95%CI: 1.0-2.9) and Metals (HR: 1.5, 95%CI: 0.9-2.8). Conclusions: Results suggest that exposure to occupational dyes or inks may influence breast cancer risk. Dyes and inks contain compounds with endocrine disrupting properties, including organic compounds and heavy metals. Further studies are necessary to elucidate the role of these potential endocrine disrupting compounds in breast cancer. Citation Format: Christine C. Ekenga. A prospective study of breast cancer risk associated with occupational exposure to potentially endocrine disrupting compounds. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-283. doi:10.1158/1538-7445.AM2014-LB-283

Sun exposure and melanoma survival: a GEM study.

We previously reported a significant association between higher UV radiation exposure before diagnosis and greater survival with melanoma in a population-based study in Connecticut. We sought to evaluate the hypothesis that sun exposure before diagnosis was associated with greater survival in a larger, international population-based study with more detailed exposure information. We conducted a multicenter, international population-based study in four countries-Australia, Italy, Canada, and the United States-with 3,578 cases of melanoma with an average of 7.4 years of follow-up. Measures of sun exposure included sunburn, intermittent exposure, hours of holiday sun exposure, hours of water-related outdoor activities, ambient ultraviolet B (280-320 nm) dose, histologic solar elastosis, and season of diagnosis. Results were not strongly supportive of the earlier hypothesis. Having had any sunburn in 1 year within 10 years of diagnosis was inversely associated with survival; solar elastosis-a measure of lifetime cumulative exposure-was not. In addition, none of the intermittent exposure measures-water-related activities and sunny holidays-were associated with melanoma-specific survival. Estimated ambient UVB dose was not associated with survival. Although there was an apparent protective effect of sunburns within 10 years of diagnosis, there was only weak evidence in this large, international, population-based study of melanoma that sun exposure before diagnosis is associated with greater melanoma-specific survival. This study adds to the evidence that sun exposure before melanoma diagnosis has little effect on survival with melanoma.

Smoking and smoking cessation effects on oncological outcomes in nonmuscle invasive bladder cancer.

Cigarette smoking is the best established risk factor for the development of bladder cancer. Nevertheless, the impact of smoking and smoking cessation on the outcomes of patients with nonmuscle invasive bladder cancer (NMIBC) remains poorly investigated. Currently, there are no prospective studies analyzing the impact of smoking on NMIBC outcomes. The majority of retrospective studies found an association between smoking status as well as cumulative lifetime exposure and disease recurrence. A recently published study demonstrated a significant impact of smoking on disease progression; however, the evidence regarding this end point is weak. There are insufficient data investigating the impact on cancer-specific and overall survival in patients with NMIBC. Assessment of the impact of smoking on particular subsets of patients with NMIBC including T1 or high-risk disease, patients receiving intravesical therapies, or sex-specific differences is limited because of a lack of data and controversial findings. Smoking cessation seems to mitigate the detrimental effects on outcomes. Although there are limited data, the growing body of evidence indicates that smoking increases the risk of disease recurrence and potentially disease progression in patients with NMIBC. Current and heavy long-term smokers seem to be at the greatest risk for both end points. Smoking cessation may limit these effects thereby improving prognosis. To improve our understanding of the associations of this important, modifiable risk factor with outcomes in patients with NMIBC, smoking should be incorporated into clinical trial design and analysis. It is the duty of each urologist to raise awareness regarding the greatest preventable cause of the development of bladder cancer, morbidity, and mortality.

Occupational exposure to extremely low-frequency magnetic fields and brain tumor risks in the INTEROCC study.

Occupational exposure to extremely low-frequency magnetic fields (ELF) is a suspected risk factor for brain tumors, however the literature is inconsistent. Few studies have assessed whether ELF in different time windows of exposure may be associated with specific histologic types of brain tumors. This study examines the association between ELF and brain tumors in the large-scale INTEROCC study. Cases of adult primary glioma and meningioma were recruited in seven countries (Australia, Canada, France, Germany, Israel, New Zealand, and the United Kingdom) between 2000 and 2004. Estimates of mean workday ELF exposure based on a job exposure matrix were assigned. Estimates of cumulative exposure, average exposure, maximum exposure, and exposure duration were calculated for the lifetime, and 1 to 4, 5 to 9, and 10+ years before the diagnosis/reference date. There were 3,761 included brain tumor cases (1,939 glioma and 1,822 meningioma) and 5,404 population controls. There was no association between lifetime cumulative ELF exposure and glioma or meningioma risk. However, there were positive associations between cumulative ELF 1 to 4 years before the diagnosis/reference date and glioma [odds ratio (OR) ≥ 90th percentile vs. < 25th percentile, 1.67; 95% confidence interval (CI), 1.36-2.07; PLinear trend < 0.0001], and, somewhat weaker associations with meningioma (OR ≥ 90th percentile vs. < 25th percentile, 1.23; 95% CI, 0.97-1.57; PLinear trend = 0.02). Results showed positive associations between ELF in the recent past and glioma. Occupational ELF exposure may play a role in the later stages (promotion and progression) of brain tumorigenesis.

Leukocyte telomere length and late-life depression.

Depressive disorders have been associated with increased risk for aging-related diseases, possibly as a consequence of accelerated cellular aging. Cellular aging, indexed by telomere length (TL) shortening, has been linked to depression in adults younger than 60 years; however, it remains unclear whether this is the case in late-life depression (age >60 years). The objective of this study was to assess differences in TL between persons with current late-life depression and never-depressed comparisons and to examine the association between characteristics of late-life depression and TL. In this cross-sectional study using the Netherlands Study of Depression in Older Persons, 355 persons with current late-life depression and 128 never-depressed comparisons, aged 60-93 years (mean age [SD]: 70.5 [7.4] years, 65% women), were recruited through primary care and mental healthcare. Late-life depression was established using a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-based structured psychiatric interview. Leukocyte TL, expressed in base pairs (bp), was determined in fasting blood samples by performing quantitative polymerase chain reaction. Mean TL did not differ between depressed persons (bp [SD]: 5,035 [431]) and never-depressed (bp [SD]: 5,057 [729]) comparisons. Further, TL was not associated with severity, duration, and age at onset of depression; comorbid anxiety disorders; anxiety symptoms; apathy severity; antidepressant use; benzodiazepine use; cognitive functioning; and childhood trauma. Late-life depression was not associated with increased cellular aging. This absent association, which contradicts observations in younger adults, may be due to the potential larger heterogenic nature of late-life depression and lifetime cumulative exposure to other TL-damaging factors, possibly overruling effects of late-life depression.

Lifetime cumulative exposure to waterpipe smoking is associated with coronary artery disease

ObjectiveGlobally, waterpipe (WP) smoking is becoming a more prevalent form of tobacco consumption. Whilst research so far has demonstrated a significant link between WP use and a number of health outcomes, little is known of its association with heart disease. We examine in this study the association of WP smoking with angiographically confirmed coronary artery disease (CAD). MethodsA total of 1210 patients, aged 40 years and over and free from smoking-associated illnesses or history of cardiovascular procedures, admitted for coronary angiography at four major hospitals in Lebanon, were included. The extent of CAD was summarized in two ways, firstly as diseased (≥50% and ≥70% occlusion in at least one main coronary artery) versus non-diseased (entirely normal coronaries), and secondly, as CAD cumulative score based on Duke CAD Prognostic Index. A score of WP-years, capturing intensity and lifetime duration of exposure, was estimated for each individual. ResultsLifetime exposure exceeding 40 WP-years was associated with a threefold significant increase in the odds of having severe stenosis (≥70%) compared to non-smokers (OR = 2.94, 95% CI 1.04–8.33) as well as with the CAD Index (β = 7.835, p-value = 0.027), net of the effect of socio-demographic characteristics, health behaviors and co-morbidity. A dose–response relationship between WP-years and percent stenosis was also established. WP smoking status (never, past and current) did not associate with CAD. ConclusionsCumulative exposure to WP smoking is significantly associated with severe CAD. There is a need to monitor WP use among cardiac patients and include this information in their medical charts in the same manner cigarettes smoking is documented. This is likely to increase awareness of the hazards of WP smoking and prompt physicians to target WP tobacco control by providing advice to their patients on WP smoking cessation.

Abstract P131: Association between Marijuana Exposure and Cognitive Function in Middle Age: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Background: Smoking marijuana is increasingly common, and understanding whether it is associated with long-term cognitive dysfunction has important implications for public health messaging. Aims: We estimated associations between cumulative exposure to marijuana and cognitive function (CF), adjusted for current marijuana use, cigarette smoking and other determinants of CF. Methods: Participants in the CARDIA Study, a population-based study of African Americans and European Americans recruited in 1985/6 at age 18-30 and followed over 25 years. Marijuana use was assessed at clinical visits at years 0, 2, 5, 7, 10, 15, 20 and 25 (2010/11); and cigarette smoking each year. Lifetime exposure to marijuana was expressed in joint-years, with 1 joint-year equivalent to smoking 365 joints. CF at year 25 was assessed with the Rey Auditory Verbal Learning Test (RAVLT), the Digit Symbol Substitution Test (DSST) and the Stroop Interference Test, each expressed as standardized z-scores. We estimated associations between current and lifetime marijuana exposure and each CF score using linear regressions, adjusted for baseline demographics, current smoking and diabetes and cumulative exposure to cigarette smoking, alcohol, illicit drugs, cardiovascular risk factors, physical activity and depression (see Table footnote). Results: Of 3385 participants with CF data, 24% had never reported marijuana use, 43% had smoked &lt;0.5 joint-year during their lifetime, 22% 0.5 to 5 joint-years and 11% ≥5 joint-years; 9% had smoked marijuana within the last 30 days. In adjusted models, current marijuana use was significantly associated with a worse RAVLT test score, but we found no association between cumulative exposure to marijuana use and CF (Table). In contrast, current and cumulative exposure to cigarette smoking were associated with lower CF. Conclusion: Cigarette smoking (current and cumulative) and current marijuana use are associated with lower CF, but we found no evidence of an association with cumulative lifetime exposure of marijuana on CF.

Radiation safety in the cardiac catheterization laboratory: Our responsibility to change

Medical radiation from x-rays and nuclear medicine is the largest manmade source of radiation exposure in Western countries, and accounts for a mean effective dose of 3.0 milliSievert (mSv) per person per year, equivalent to the radiological risk of 150 chest x-rays. Of these, 0.43 mSv come from interventional radiology (0.20 mSv) and interventional cardiology (0.23 mSv). Among adult cardiology patients, fluoroscopically-guided diagnosis and intervention account for 12% of all radiological examinations performed, and 48% of their total collective dose. On average, a diagnostic invasive angiogram corresponds to a patient radiation exposure of about 7 mSv (range 2-16), while coronary stenting corresponds to 15 mSv (range 7-57). Progressively higher effective doses are observed for transcutaneous aortic valvuloplasty (39 mSv), dilation of total occlusion of coronary arteries (81 mSv, range 17-194) and endovascular thoraco-abdominal aneurysm repair procedure (76-190 mSv). Most experienced (and most exposed) interventional cardiologists have an exposure per annum of around 5 mSv, two to three times higher than diagnostic radiologists, with a typical cumulative lifetime cumulative exposure around 100 mSv and attributable risk in the order of magnitude of 1 cancer (fatal and non-fatal) per 100 exposed subjects. However, adequate radiation protection training and diligent protection can reduce this radiation exposure by 90%. Attention to radiation protection is one aspect - and not the least important - of good practice of interventional cardiology.

Menarche, menopause, years of menstruation, and the incidence of osteoporosis: the influence of prenatal exposure to diethylstilbestrol.

Estrogen is critical for bone formation and growth in women. Estrogen exposures occur throughout life, including prenatally, and change with reproductive events, such as menarche and menopause. The objective of this study was to investigate the association between age at menarche, age at menopause, and years of menstruation with incidence of osteoporosis and assess the impact of prenatal exposure to diethylstilbestrol (DES), a synthetic estrogen, on such associations. Participants were 5573 women in the National Cancer Institute Combined Cohort Study of DES (1994-2006). Data on reproductive history and medical conditions were collected through questionnaires at baseline in 1994 and subsequently in 1997, 2001, and 2006. Age-stratified Cox regression models were used to calculate multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Effect measure modification by prenatal DES exposure was assessed using cubic restricted spline regression models. Osteoporosis was the main outcome measure. The IRRs for osteoporosis incidence with age at menarche less than 11 years and age at menopause of 50 years or younger were 0.82 (CI 0.59, 1.14) and 0.61 (CI 0.40, 0.92), respectively. Fewer than 25 years of menstruation was associated with an increased incidence of osteoporosis (IRR 1.80; CI 1.14, 2.86) compared with 35 years or more of menstruation. Associations were stronger among women who had not been prenatally exposed to DES. Our data support the hypothesis that lifetime cumulative exposure to estrogens is protective against osteoporosis. Furthermore, prenatal exposure to estrogen appears to modify these associations, although the mechanism by which this occurs is unknown.

Children with nephrotic syndrome have greater bone area but similar volumetric bone mineral density to healthy controls

BackgroundGlucocorticoid use has been associated with an increased fracture risk and reduced bone mineral density (BMD), particularly in the trabecular compartment. However the contribution of the underlying inflammatory disease process to these outcomes is poorly understood. Childhood nephrotic syndrome (NS) typically follows a relapsing–remitting course often requiring recurrent courses of glucocorticoids, but with low systemic inflammation during remission. NS therefore represents a useful clinical model to investigate the effects of glucocorticoids on BMD and bone geometry in childhood. MethodsChildren with NS were compared to age and sex matched healthy controls. Body composition and areal BMD (whole body, lumbar spine and hip) were assessed by DXA. Peripheral quantitative computed tomography (pQCT) scans were obtained at metaphyseal (4%) and diaphyseal (66%) sites of the tibia to determine volumetric BMD and bone cross-sectional geometry. Lifetime cumulative glucocorticoid exposure was calculated from medical records. Results29 children with NS (55% male, age 10.7±3.1years) were compared to 29 healthy controls (55% male, age 11.0±3.0years). The children with NS were of similar height SDS to controls (p=0.28), but were heavier (0.65±1.28SDS vs −0.04±0.89SDS, p=0.022) and had greater body fat percentage SDS (0.31±1.01 vs −0.52±1.10, p=0.008). Tibial trabecular and cortical vBMD were similar between the two groups but bone cross-sectional area (CSA) was significantly greater in children with NS at both the metaphysis (954±234mm2 vs 817±197mm2, p=0.002) and diaphysis (534.9±162.7mm2 vs 463.2±155.5mm2, p=0.014). Endosteal and periosteal circumferences were greater in children with NS than controls (both p<0.01), resulting in reduced cortical thickness (2.4±0.7mm vs 2.8±0.7mm, p=0.018), but similar cortical CSA (p=0.22). The differences in cortical geometry were not statistically significant when weight was included as a confounding factor. There were no associations between cumulative steroid exposure, duration of NS or number of relapses and any bone parameter. ConclusionsTibial bone CSA is increased in children with NS. We speculate that this is a compensatory response to increased body weight. Defects in trabecular BMD were not identified in this cohort of children with NS.

104 Association between occupational exposure to engine emissions and lung cancer

ObjectiveTo analyse the associations between life-time occupational exposures to diesel, leaded and unleaded gasoline engine emissions and lung cancer.MethodsOur case-control study enrolled 1503 lung cancer cases and 1198 population controls...

INTEROCC case–control study: lack of association between glioma tumors and occupational exposure to selected combustion products, dusts and other chemical agents

BackgroundThe aim was to investigate possible associations between glioma (an aggressive type of brain cancer) and occupational exposure to selected agents: combustion products (diesel and gasoline exhaust emissions, benzo(a)pyrene), dusts (animal dust, asbestos, crystalline silica, wood dust) and some other chemical agents (formaldehyde, oil mist, sulphur dioxide).MethodsThe INTEROCC study included cases diagnosed with glioma during 2000–2004 in sub-regions of seven countries. Population controls, selected from various sampling frames in different centers, were frequency or individually matched to cases by sex, age and center. Face-to-face interviews with the subject or a proxy respondent were conducted by trained interviewers. Detailed information was collected on socio-economic and lifestyle characteristics, medical history and work history. Occupational exposure to the 10 selected agents was assessed by a job exposure matrix (JEM) which provides estimates of the probability and level of exposure for different occupations. Using a 25% probability of exposure in a given occupation in the JEM as the threshold for considering a worker exposed, the lifetime prevalence of exposure varied from about 1% to about 15% for the different agents. Associations between glioma and each of the 10 agents were estimated by conditional logistic regression, and using three separate exposure indices: i) ever vs. never; ii) lifetime cumulative exposure; iii) total duration of exposure.ResultsThe study sample consisted of 1,800 glioma cases and 5,160 controls. Most odds ratio estimates were close to the null value. None of the ten agents displayed a significantly increased odds ratio nor any indication of dose–response relationships with cumulative exposure or with duration of exposure.ConclusionThus, there was no evidence that these exposures influence risk of glioma.

Impact of Smoking and Smoking Cessation on Outcomes in Bladder Cancer Patients Treated with Radical Cystectomy

BackgroundCigarette smoking is the best-established risk factor for urothelial carcinoma development. ObjectiveTo elucidate the association of pretreatment smoking status, cumulative exposure, and time since smoking cessation on outcomes of patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC). Design, setting, and participantsWe retrospectively collected clinicopathologic and smoking variables, including smoking status, number of cigarettes per day (CPD), duration in years, and time since smoking cessation, for 1506 patients treated with RC for UCB. Lifetime cumulative smoking exposure was categorized as light short-term (≤20 CPD for ≤20 yr), light long-term (≤20 CPD for >20 yr), heavy short-term (>20 CPD for ≤20 yr), and heavy long-term (>20 CPD for >20 yr). InterventionRC and bilateral lymph node (LN) dissection without neoadjuvant chemotherapy. Outcome measurements and statistical analysisLogistic regression and competing risk analyses assessed the association of smoking with disease recurrence, cancer-specific mortality, and overall mortality. Results and limitationsThere was no difference in clinicopathologic factors between patients who had never smoked (20%), former smokers (46%), and current smokers (34%). Smoking status was associated with the cumulative incidence of disease recurrence (p=0.004) and cancer-specific mortality (p=0.016) in univariable analyses and with disease recurrence in multivariable analysis (p=0.02); current smokers had the highest cumulative incidences. Among ever smokers, cumulative smoking exposure was associated with advanced tumor stages (p<0.001), LN metastasis (p=0.002), disease recurrence (p<0.001), cancer-specific mortality (p=0.001), and overall mortality (p=0.037) in multivariable analyses that adjusted for standard characteristics; heavy long-term smokers had the worst outcomes, followed by light long-term, heavy short-term, and light short-term smokers. Smoking cessation ≥10 yr mitigated the risk of disease recurrence (hazard ratio [HR]: 0.44; p<0.001), cancer-specific mortality (HR: 0.42; p<0.001), and overall mortality (HR: 0.69; p=0.012) in multivariable analyses. The study is limited by its retrospective nature. ConclusionsSmoking is associated with worse prognosis after RC for UCB. This association seems to be dose-dependent, and its effects are mitigated by >10 yr smoking cessation. Health care practitioners should counsel smokers regarding the detrimental effects of smoking and the benefits of smoking cessation on UCB etiology and prognosis.

Impact of Smoking and Smoking Cessation on Oncologic Outcomes in Primary Non–muscle-invasive Bladder Cancer

BackgroundCigarette smoking is the best-established risk factor for urothelial carcinoma (UC) development, but the impact on oncologic outcomes remains poorly understood. ObjectiveTo analyse the effects of smoking status, cumulative exposure, and time from smoking cessation on the prognosis of patients with primary non–muscle-invasive bladder cancer (NMIBC). Design, setting, and participantsWe collected smoking data from 2043 patients with primary NMIBC. Smoking variables included smoking status, average number of cigarettes smoked per day (CPD), duration in years, and time since smoking cessation. Lifetime cumulative smoking exposure was categorised as light short term (≤19 CPD, ≤19.9 yr), light long term (≤19 CPD, ≥20 yr), heavy short term (≥20 CPD, ≤19.9 yr) and heavy long term (≥20 CPD, ≥20 yr). The median follow-up in this retrospective study was 49 mo. InterventionsTransurethral resection of the bladder with or without intravesical instillation therapy. Outcome measurements and statistical analysisUnivariable and multivariable logistic regression and competing risk regression analyses assessed the effects of smoking on outcomes. Results and limitationsThere was no difference in clinicopathologic factors among never (24%), former (47%), and current smokers (29%). Smoking status was associated with the cumulative incidence of disease progression in multivariable analysis (p=0.003); current smokers had the highest cumulative incidences. Among current and former smokers, cumulative smoking exposure was associated with disease recurrence (p<0.001), progression (p<0.001), and overall survival (p<0.001) in multivariable analyses that adjusted for the effects of standard clinicopathologic factors and smoking status; heavy long-term smokers had the worst outcomes, followed by light long-term, heavy short-term, and light short-term smokers. Smoking cessation >10 yr reduced the risk of disease recurrence (hazard ratio [HR]: 0.66; 95% confidence interval [CI], 0.52–0.84; p<0.001) and progression (HR: 0.42; 95% CI, 0.22–0.83; p=0.036) in multivariable analyses. The study is limited by its retrospective nature. ConclusionsSmoking status and a higher cumulative smoking exposure are associated with worse prognosis in patients with NMIBC. Smoking cessation >10 yr abrogates this detrimental effect. These findings underscore the need for integrated smoking cessation and prevention programmes in the management of NMIBC patients.

A proposed methodology to estimate the cumulative life-time UVB exposure using geographic information systems: An application to multiple sclerosis

BackgroundThe cause of multiple sclerosis (MS) is unknown; multiple risk factors have been implicated, including environmental exposures, such as sunlight. Many studies have relied on latitude alone as a crude proxy for sunlight exposure. We aimed to develop a protocol allowing a more detailed estimate of cumulative ambient ultra-violet B (UVB) exposure at critical time-periods over a patient's life-course. Methods4010 definite MS patients with a ‘movement history’ from birth to the study end (2005) were selected from the University of British Columbia, Canada's MS Genetic database. Patient's place of resident from birth were tracked, each place being geocoded (latitude and longitude) and assigned a UVB value using the NASA Total Ozone Mapping Spectrometer (TOMS) dataset. Combined, these data allowed an estimated UVB value for each patient based on year and location. ResultsUsing this protocol, we provide a potentially more detailed cumulative UVB exposure for critical periods in a patients' life history based on their individual spatial migration through time. ConclusionsThis protocol is intended to provide a framework for researchers to more accurately estimate UVB exposures for individuals over the course of their life history and may be useful for understanding etiology of MS and other chronic disease.